We are investigating the kinetics and chemistry of isoenzymes of yeast alcohol dehydrogenase which have been produced by mutation and selection in our laboratory. It is our hope that these investigations will lead to a better understanding of the function of this and other enzyme molecules, through a determination of which amino acid substitutions will lead to particular kinetic alterations. We also hope to answer questions of general evolutionary interest, such as: in how many ways can an enzyme molecule change as a selective response to a given environmental alteration, and what fraction of the molecule is potentially involved in this change? Our mutant enzymes, some of which have manyfold changes in Km and Vmax, have been produced by selection for resistance to allyl alcohol. The mutants are resistant because of a shift in the NAD-NADH balance in the cell, which in turn shifts the equilibrium between allyl alcohol and its poisonous product acrolein. BIBLIOGRAPHIC REFERENCES: Wills, C., Phelps, J., and R. Ferguson. 1975. Further Evidence for Selective Differences Between Isoalleles In Drosophila. Genetics 79:127-141. Wills, C., and J. Phelps. 1975. A technique for the Isolation of Yeast Alcohol Dehydrogenase Mutants with Altered Substrate Specificity. Arch. Biochem. Biophy. 167 627-637.